Pecans and Its Polyphenols Prevent Obesity, Hepatic Steatosis and Diabetes by Reducing Dysbiosis, Inflammation, and Increasing Energy Expenditure in Mice Fed a High-Fat Diet.

Pecans (Carya illinoinensis) are considered a functional food due to the high content of polyunsaturated fatty acids, dietary fiber and polyphenols. To determine the effect of whole pecans (WP) or a pecan polyphenol (PP) extract on the development of metabolic abnormalities in mice fed a high-fat (HF) diet, we fed C57BL/6 mice with a Control diet (7% fat), HF diet (23% fat), HF containing 30% WP or an HF diet supplemented with 3.6 or 6 mg/g of PP for 18 weeks. Supplementation of an HF diet with WP or PP reduced fat mass, serum cholesterol, insulin and HOMA-IR by 44, 40, 74 and 91%, respectively, compared to the HF diet. They also enhanced glucose tolerance by 37%, prevented pancreatic islet hypertrophy, and increased oxygen consumption by 27% compared to the HF diet. These beneficial effects were associated with increased thermogenic activity in brown adipose tissue, mitochondrial activity and AMPK activation in skeletal muscle, reduced hypertrophy and macrophage infiltration of subcutaneous and visceral adipocytes, reduced hepatic lipid content and enhanced metabolic signaling. Moreover, the microbial diversity of mice fed WP or PP was higher than those fed HF, and associated with lower circulating lipopolysaccharides (~83-95%). Additionally, a 4-week intervention study with the HF 6PP diet reduced the metabolic abnormalities of obese mice. The present study demonstrates that WP or a PP extract prevented obesity, liver steatosis and diabetes by reducing dysbiosis, inflammation, and increasing mitochondrial content and energy expenditure. Pecan polyphenols were mainly condensed tannin and ellagic acid derivatives including ellagitannins as determined by LC-MS. Herein we also propose a model for the progression of the HF diet-mediated metabolic disorder based on early and late events, and the possible molecular targets of WP and PP extract in preventive and intervention strategies. The body surface area normalization equation gave a conversion equivalent to a daily human intake dose of 2101-3502 mg phenolics that can be obtained from 110-183 g pecan kernels/day (22-38 whole pecans) or 21.6-36 g defatted pecan flour/day for an average person of 60 kg. This work lays the groundwork for future clinical studies.

Vachellia farnesiana Pods or a Polyphenolic Extract Derived from Them Exert Immunomodulatory, Metabolic, Renoprotective, and Prebiotic Effects in Mice Fed a High-Fat Diet.

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.

Reviewing the Benefits of Grazing/Browsing Semiarid Rangeland Feed Resources and the Transference of Bioactivity and Pro-Healthy Properties to Goat Milk and Cheese: Obesity, Insulin Resistance, Inflammation and Hepatic Steatosis Prevention.

The rangeland is an ecological resource that provides multiple benefits for environment and agriculture. Grazing/browsing on rangelands is a useful and inexpensive means to produce food derived from animal products. The aim of this study was to review the benefits of producing milk and cheese under this system in terms of bioactivity and the health benefits of their consumption in model animals. To conduct this review, we particularly considered the experiments that our research group carried out along the last fifteen years at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico. Firstly, we examined the forages consumed by goats on the rangelands in terms of plant bioactive compound occurrence and their concentration. Further, goat milk and cheese coming from (1) grazing animals, (2) animals managed indoors, and from (3) animals managed indoor supplemented with rich plant bioactive compounds, were analyzed. Milk was discussed to modulate the negative effects of high-fat diets in mice. Forages consumed by goats on the rangelands showed a close correlation between antioxidant activity assessed by the DPPH+ radical with total flavonoid and total polyphenol contents (TPC). Milk concentration of PUFA, MUFA, and n-3 fatty acids from grazing goats (4.7%, 25.2%, and 0.94% of FAME) was higher than milk from goats fed indoor diets (ID). Similar results were shown in cheese. TPC was higher in cheese manufactured with milk from grazing goats (300 mg of GAE/kg of cheese) when compared to cheese from milk goats fed ID (60 mg of GAE/of cheese). Acacia pods are a semiarid rangeland feed resource that transfers pro-healthy activity, inhibited in vitro lipid peroxidation (inhibition of TBARS formation) and diminished the damage induced by reactive oxygen species (ROS). Additionally, in vivo assessment revealed that Acacia species increased free radical scavenging (DPPH), oxygen radical absorbance capacity, and anti-inflammatory activity. The results highlight that grazing/browsing practices are superior to indoor feeding in order to promote the transference of bioactive compounds from vegetation to animal tissue, and finally to animal products. Grazing management represents a better option than indoor feeding to enhance bioactivity of milk and cheese. Supplementation with rich-bioactive compound forages increased total polyphenol, hydroxycinnamic acids, and flavonoid concentrations in milk and cheese. The consumption of goat milk prevents obesity, insulin resistance, inflammation, and hepatic steatosis while on a high-fat diet induced obesity in mice.

Goat's Milk Intake Prevents Obesity, Hepatic Steatosis and Insulin Resistance in Mice Fed A High-Fat Diet by Reducing Inflammatory Markers and Increasing Energy Expenditure and Mitochondrial Content in Skeletal Muscle.

Goat's milk is a rich source of bioactive compounds (peptides, conjugated linoleic acid, short chain fatty acids, monounsaturated and polyunsaturated fatty acids, polyphenols such as phytoestrogens and minerals among others) that exert important health benefits. However, goat's milk composition depends on the type of food provided to the animal and thus, the abundance of bioactive compounds in milk depends on the dietary sources of the goat feed. The metabolic impact of goat milk rich in bioactive compounds during metabolic challenges such as a high-fat (HF) diet has not been explored. Thus, we evaluated the effect of milk from goats fed a conventional diet, a conventional diet supplemented with 30% Acacia farnesiana (AF) pods or grazing on metabolic alterations in mice fed a HF diet. Interestingly, the incorporation of goat's milk in the diet decreased body weight and body fat mass, improved glucose tolerance, prevented adipose tissue hypertrophy and hepatic steatosis in mice fed a HF diet. These effects were associated with an increase in energy expenditure, augmented oxidative fibers in skeletal muscle, and reduced inflammatory markers. Consequently, goat's milk can be considered a non-pharmacologic strategy to improve the metabolic alterations induced by a HF diet. Using the body surface area normalization method gave a conversion equivalent daily human intake dose of 1.4 to 2.8 glasses (250 mL per glass/day) of fresh goat milk for an adult of 60 kg, which can be used as reference for future clinical studies.

Ellagic Acid and Urolithins A and B Differentially Regulate Fat Accumulation and Inflammation in 3T3-L1 Adipocytes While Not Affecting Adipogenesis and Insulin Sensitivity.

Ellagic acid (EA) is a component of ellagitannins, present in crops such as pecans, walnuts, and many berries, which metabolized by the gut microbiota forms urolithins A, B, C, or D. In this study, ellagic acid, as well as urolithins A and B, were tested on 3T3-L1 preadipocytes for differentiation and lipid accumulation. In addition, inflammation was studied in mature adipocytes challenged with lipopolysaccharide (LPS). Results indicated that EA and urolithins A and B did not affect differentiation (adipogenesis) and only EA and urolithin A attenuated lipid accumulation (lipogenesis), which seemed to be through gene regulation of glucose transporter type 4 (GLUT4) and adiponectin. On the other hand, gene expression of cytokines and proteins associated with the inflammation process indicate that urolithins and EA differentially inhibit tumor necrosis factor alpha (TNFα), inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Urolithins A and B were found to reduce nuclear levels of phosphorylated nuclear factor κB (p-NF-κB), whereas all treatments showed expression of nuclear phosphorylated protein kinase B (p-AKT) in challenged LPS cells when treated with insulin, indicating the fact that adipocytes remained insulin sensitive. In general, urolithin A is a compound able to reduce lipid accumulation, without affecting the protein expression of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (c/EBPα), and PPARα, whereas EA and urolithin B were found to enhance PPARγ and c/EBPα protein expressions as well as fatty acid (FA) oxidation, and differentially affected lipid accumulation.

Extensive Ruminant Production Systems and Milk Quality with Emphasis on Unsaturated Fatty Acids, Volatile Compounds, Antioxidant Protection Degree and Phenol Content.

Dairy products from grazing ruminant have numerous positive effects on human health thanks to their higher content essential fatty acids, vitamins, and polyphenols. Compared to livestock fed a conventional maize silage- and/or grain-based diet, grass-fed livestock produce milk with higher levels of n-3 fatty acids, vitamins A, E, carotenoids, and phenols. The effect is even more pronounced if animals are grazing on legume/forbs-rich grasslands. This review argues, based on the available literature, about the effect of grazing ruminant on milk and cheese quality, including the hedonistic aspects, pointing out the link between territory and dairy products quality (Protected Designation Origin; Protected Geografic Origin; namely PDO and PGI labels). Moreover, it points out the main plant biomarkers which can be used to discriminate grazing sourced from stall-fed sourced milk and dairy products. Overall milk and cheese sourced from grazing animals (cows, sheep and goat) showed higher levels (compared to stall system) of FA, vitamins, phenols, putatively beneficial for consumers' health. FA and plant secondary metabolites can also affect flavor and some nutritional and technological features of dairy products such as their antioxidant protection degree. This would favour a fair pricing of dairy products sourced from grazing systems and the persistence of viable and sustainable extensive production systems.

Goats' Feeding Supplementation with Acacia farnesiana Pods and Their Relationship with Milk Composition: Fatty Acids, Polyphenols, and Antioxidant Activity.

BACKGROUND: Research efforts have focused on the evaluation of the bioactive quality of animal products (milk, cheese, meat, and other by-products) contrasting various feeding strategies coming from different ecological zones. The study aimed to describe the fatty acids (FA), polyphenols (P), bioactive compounds (BC), and antioxidant activity (AA) of goat's milk. METHODS: Dairy goats were fed with five systems: (1) Grazing; (2) conventional diet (CD); (3) CD + 10% of Acacia farnesiana (AF) pods; (4) CD + 20% AF; and (5) CD + 30% AF. The fatty acid profile, health promoting and thrombogenic indexes were calculated. Milk extracts were evaluated by HPLC to determent phenolic compounds (gallic, caffeic, chlorogenic, and ferulic acids, catechin, epicatechin, and quercetin). Antioxidant activity of goat's milk extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•), oxygen radical absorbance capacity (ORAC), and the ferric reducing antioxidant power (FRAP) assays. RESULTS: Conventional diet showed the highest content of polyunsaturated fatty acids while grazing showed the best n-6:n-3 and the linoleic:alpha linolenic acid ratio. Similarly, grazing and AF boosted the polyphenol content. CONCLUSIONS: Acacia farnesiana inclusion in the goats' diets increased the presence of bioactive compounds and the antioxidant activity while diminishing the cholesterol content of goat's milk.